Expeditious syntheses of stable and radioactive isotope‐labeled anticonvulsant agent, JNJ‐26990990, and its metabolites. (10th January 2013)

• Record Type: Journal Article
• Authors: Lin, Ronghui; Weaner, Larry E.; Hoerr, David C.; Salter, Rhys; Gong, Yong
• Is Part Of: Journal of labelled compounds & radiopharmaceuticals. Volume 56:Number 1(2013)
• Page Start: 22
• Page End: 26
• Publication Date: 2013-01-10
• Subjects: Tracers (Chemistry) -- Periodicals; Radiopharmaceuticals -- Periodicals; 615.8424
• DOI: 10.1002/jlcr.3013
• Languages: English
• ISSNs: 0362-4803

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Syntheses of stable and radioactive isotope‐labeled anticonvulsant agent, JNJ‐26990990, that is, <italic>N</italic>‐(benzo[b]thien‐3‐ylmethyl)‐sulfamide and its metabolites are described. [¹³C¹⁵N]Benzo[b]thiophene‐3‐carbonitrile was first prepared by coupling of 3‐bromo‐benzo[b]thiophene with [¹³C¹⁵N]‐copper cyanide. The resultant [¹³C¹⁵N]benzo[b]thiophene‐3‐carbonitrile was reduced with lithium aluminum deuteride to give [¹³CD₂¹⁵N]benzo[b]thiophen‐3‐yl‐methylamine; which was then coupled with sulfamide to afford [¹³CD₂¹⁵N]‐<italic>N</italic>‐(benzo[b]thien‐3‐ylmethyl)‐sulfamide, the stable isotope‐labeled compound with four stable isotope atoms. Direct oxidation of [¹³CD₂¹⁵N]‐<italic>N</italic>‐(benzo[b]thien‐3‐ylmethyl)‐sulfamide with hydrogen peroxide and peracetic acid gave the stable isotope‐labeled sulfoxide and sulfone metabolites. On the other hand, radioactive ¹⁴C‐labeled <italic>N</italic>‐(benzo[b]thien‐3‐ylmethyl)‐sulfamide was prepared conveniently by sequential coupling of 3‐bromo‐benzo[b]thiophene with [¹⁴C]‐copper cyanide, reduction of the carbonitrile to carboxaldehyde, and reductive amination with sulfamide.</p> </abstract>